Format

Send to

Choose Destination
J Cell Sci. 2018 Oct 11. pii: jcs.219956. doi: 10.1242/jcs.219956. [Epub ahead of print]

AAA ATPase Afg1 preserves organellar fidelity and cellular healthspan by maintaining mitochondrial matrix proteostasis.

Author information

1
Department of Biochemistry, Nebraska Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.
2
Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424, USA.
3
Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424, USA okhalimonchuk2@unl.edu foxjl@cofc.edu.
4
Department of Biology, Aging Mind and Brain Initiative, University of Iowa, Iowa City, IA 52242, USA.
5
Department of Biochemistry, Nebraska Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA okhalimonchuk2@unl.edu foxjl@cofc.edu.
6
Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Abstract

Mitochondrial functions are critical for cellular physiology; therefore, several conserved mechanisms are in place to maintain the functional integrity of mitochondria. However, many of the molecular details and components involved in ensuring mitochondrial fidelity remain obscure. Here we identify a novel role for the conserved mitochondrial AAA ATPase Afg1 in mediating mitochondrial protein homeostasis during aging and in response to various cellular challenges. Saccharomyces cerevisiae cells lacking functional Afg1 are hypersensitive to oxidative insults, unable to tolerate protein misfolding in the matrix compartment, and exhibit progressive mitochondrial failure as they age. Loss of Afg1 ortholog LACE-1 in Caenorhabditis elegans is associated with reduced lifespan, impeded oxidative stress tolerance, impaired mitochondrial proteostasis in motor neuron circuitry, and altered behavioral plasticity. Our results indicate that Afg1 is a novel protein quality control factor, which plays an important evolutionarily conserved role in mitochondrial surveillance and cellular and organismal healthspan.

KEYWORDS:

C. elegans; LACE-1; Mitochondria; Mitochondrial fidelity; Protein homeostasis; Yeast

PMID:
30301782
DOI:
10.1242/jcs.219956

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center